Numerous illnesses are caused by excessive levels of harmful agents in the blood stream. Two large classes of such disturbances include those which are associated with:
(1) Substances in toxic excess concentrations, such as externally derived drugs, e.g. digoxin, gentamicin, etc. and internally derived substances, e.g. thyroxin in thyrotoxicosis, etc.; or PA1 (2) Abnormal auto-antibodies which are directed against normal tissue constituents, such as rheumatoid factor, anti-DNA, etc.
In some of these disturbances, particularly the latter group, recent studies have indicated that plasmapheresis exerts a beneficial therapeutic effect, apparently as a cleansing mechanism. However, plasmapheresis is a relatively crude method of removing unwanted deleterious substances, since it results in the depletion of virtually all plasma constituents, including many essential beneficial ones, in addition to the removal of the harmful agent. Ideally, a highly selective system is required which removes only the unwanted harmful agent, and leaves all the other plasma constituents unchanged in the patient. The resultant therapeutic effects would presumably be considerably more efficient and thorough, with no side effects due to the treatment.
Only one approach with the required high degree of selectivity is presently known. This approach involves immunological reagents (antibodies, antigens or haptens), which have been shown to possess remarkable degrees of specificity. The use of such reagents in solid phase has proven feasible in numerous demonstrations during the last 10 to 20 years. Thus, it has been established in the art that antibodies and antigens can be bound covalently to solid supports in a fully reactive state while retaining complete specificity. This "solid phase" technology is the basis for a large proportion of the sensitive radio-immunoassays and enzyme-immunoassays currently used in diagnostic laboratories.
The prior art literature reveals several suggested therapeutic methodologies employing solid-phase immunoadsorbent columns. Where the immunoadsorbent is adsorbed on a solid phase such as activated charcoal, there exists the possibility of leakage of the immunoadsorbent into the blood which might provoke an immune response within the patient, thus producing undesirable side effects. Even where such prior art columns have employed immunoadsorbents covalently bound to a particulate solid substrate, the column performance in the treatment of blood has proven to be less than entirely satisfactory, for use as a shunt between an artery and vein, because of the tendency of the packed column to become plugged. Another approach suggested in the literature is the use of an extracorporeal shunt in the form of a chamber containing a number of polymethylmethacrylate plates to which a proteinaceous immunoadsorbent is covalently bound. See: Holger Hyden "Enzyme Therapy and Immuno-adsorption by an Extra-Corporeal Device"; Biomat.Med.Art.Org., 1980,8,(1), pp. 1-11. The limitations imposed by the use of such a device relate to the limited amount of surface area with bound immunoadsorbent and facility for regeneration.
Ideally, any extracorporeal shunt should be of a nature which allows therapeutic treatment to be conducted continuously over as long a period of time as is appropriate to the patient's condition. Accordingly, it is an object of the present invention to provide a therapeutic device having a solid phase immobilized immunoadsorbent specific for a harmful agent to be removed from blood, blood plasma or serum and of a nature which permits continuous, prolonged use as an extracorporeal shunt when connected between an artery and vein of a patient.
Consistent with the aforementioned objective, it is a further objective of the present invention to provide such a device which may be easily and rapidly regenerated without interruption of therapeutic treatment.
It is yet another object of the present invention to provide a relatively large surface area of bound immunoadsorbent relative to the volumetric flow rate of the blood undergoing treatment.
Yet another object of the invention is to provide such a device characterized by minimal pressure drop and susceptibility to plugging.
These and other objects and features of the present invention will become apparent to those skilled in the art from a reading of the description which follows in conjunction with the accompanying drawing.